Personalized medicine holds the promise that the diagnosis, prevention and treatment of cancer will be based on individual assessment of risk (Dalton and Friend, Science 2006; 312(5777):1165-8). The delivery of this promise in radiation oncology is dependent on the ability to define the variables that define response to clinical radiotherapy. Although most strategies in personalized medicine have focused on specific disease sites and/or drug therapies (van 't Veer et al., Nature 2002; 415(6871):530-6; Beer et al., Nat Med 2002; 8(8):816-24; Chung et al., Cancer Cell 2004; 5(5):489-500; Eschrich et al., J Clin Oncol 2005; 23(15):3526-35; Giles et al., Semin Oncol 2008; 35 (1 Suppl 1):S1-17), the impact of individualizing radiation therapy is significant. Approximately 60% of cancer patients are treated with radiation therapy during their diagnosis (Perez, Principles and Management of Radiation Therapy. Philadelphia-New York: Lippincott-Raven; 1998). Thus, radiation therapy provides a common denominator in cancer therapeutics.
Significant advances towards personalized radiation therapy have been largely achieved by physical advances in radiotherapy treatment planning and delivery (Bucci et al., CA Cancer J Clin 2005; 55(2):117-34). In contrast, the efforts in understanding the biological parameters that define intrinsic radiosensitivity have not met the same success. Thus, radiotherapy is prescribed without considering the potential individual differences in tumor and patient radiosensitivity. However there is evidence to suggest that differences in intrinsic radiosensitivity exist (Zelefsky et al., J. Urology 2001; 166(3):876-81) and understanding their biological basis could significantly impact clinical practice. Thus, a successful radiosensitivity predictive assay would be central to the development of biologically-guided personalized treatment strategies in radiation oncology. However, although a number of promising approaches have been developed in the past (e.g., determination of ex-vivo tumor SF2, (Bjork-Eriksson et al., Int J Radiat Oncol Biol Phys 2000; 46(1):13-9; Buffa et al., Int J Radiat Oncol Biol Phys 2001; 50(5):1113-22; Eschwege et al., Int J Radiat Oncol Biol Phys 1997; 39(4):849-53; Taghian et al., Int J Radiat Oncol Biol Phys 1993; 25(2):243-9; West et al., British Journal of Cancer 1997; 76(9):1184-90; West et al., Br J Cancer 1993; 68(4):819-23); the use of electrodes to measure tumor hypoxia (Fyles et al., J Clin Oncol 2002; 20(3):680-7; Movsas et al., Urology 2002; 60(4):634-9); and determination of tumor proliferative potential (Tpot) (Begg et al., Radiother Oncol 1999; 50(1):13-23; Bourhis et al., Int J Radiat Oncol Biol Phys 1996; 35(3):471-6; Corvo et al., J Clin Oncol 1995; 13(8):1843-50), none has become routine in the clinic.